The DOI matches its Crossref record; 74 of the 75 references it cites were found in a registry or an index.
Phosphodiesterase-4 (PDE4) Molecular Pharmacology and Alzheimer's Disease
Open accessAbstract
Between 20% and 25% of patients diagnosed with Alzheimer's disease (AD) do not have amyloid burden as assessed by positron emission tomography imaging. Thus, there is a need for nonamyloid-directed therapies for AD, especially for those patients with non-amyloid AD. The family of phosphodiesterase-4 (PDE4) enzymes are underexploited therapeutic targets for central nervous system indications. While the PDE4A, B, and D subtypes are expressed in brain, the strict amino acid sequence conservation of the active site across the four subtypes of PDE4 has made it difficult to discover subtype inhibitors. The recent elucidation of the structure of the PDE4 N- and C-terminal regulatory domains now makes it possible to design subtype-selective, negative allosteric modulators (PDE4-NAMs). These act through closing the N-terminal UCR2 or C-terminal CR3 regulatory domains, and thereby inhibit the enzyme by blocking access of cyclic adenosine monophosphate (cAMP) to the active site. PDE4B-NAMs have the potential to reduce neuroinflammation by dampening microglia cytokine production triggered by brain amyloid, while PDE4D-NAMs have potent cognitive benefit by augmenting signaling through the cAMP/protein kinase A/cAMP response element-binding protein (CREB) pathway for memory consolidation. The importance of PDE4D for human cognition is underscored by the recent discovery of PDE4D mutations in acrodysostosis (ACRDY2: MIM 600129), an ultra rare disorder associated with intellectual disability. Thus, the family of PDE4 enzymes provides rich opportunities for the development of mechanistically novel drugs to treat neuroinflammation or the cognitive deficits in AD.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The APP/PS1 mouse model of AD develops long-term potentiation (LTP) deficits, but rolipram-treated APP/PS1 mice showed comparable LTP induction to wild-type animals85.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [85]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404
Goate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051
Hearing loss and cognitive decline in older adults
Lin, F. R., Yaffe, K., Xia, J., Xue, Q.-L., Harris, T. B., Purchase-Helzner, E., Satterfield, S., Ayonayon, H. N., Ferrucci, L., Simonsick, E. M., et al. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.1868 · Cited by 4,017
Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599
Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease
Salloway, S., Sperling, R., Fox, N. C., Blennow, K., Klunk, W., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., Ferris, S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1304839 · Cited by 1,960
A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline
Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., et al. (2012) · Nature · doi:10.1038/nature11283 · Cited by 1,738
Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease
Doody, R. S., Thomas, R. G., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., Raman, R., Sun, X., Aisen, P. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1312889 · Cited by 1,668
Purification and cloning of amyloid precursor protein β-secretase from human brain
Sinha, S., Anderson, J. P., Barbour, R., Basi, G. S., Caccavello, R., Davis, D., Doan, M., Dovey, H. F., Frigon, N., Hong, J., et al. (1999) · Nature · doi:10.1038/990114 · Cited by 1,612
Mullan, M., Crawford, F., Axelman, K., Houlden, H., Lilius, L., Winblad, B., & Lannfelt, L. (1992) · Nature Genetics · doi:10.1038/ng0892-345 · Cited by 1,513
Monetary Costs of Dementia in the United States
Hurd, M. D., Martorell, P., Delavande, A., Mullen, K. J., & Langa, K. M. (2013) · New England Journal of Medicine · doi:10.1056/nejmsa1204629 · Cited by 1,484
Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity
Yan, R., Bienkowski, M. J., Shuck, M. E., Miao, H., Tory, M. C., Pauley, A. M., Brashler, J. R., Stratman, N. C., Mathews, W. R., Buhl, A. E., et al. (1999) · Nature · doi:10.1038/990107 · Cited by 1,438
Self-citationA mutation in the Amyloid Precursor Protein Associated with Hereditary Alzheimer's Disease
Murrell, J. R., Farlow, M. R., Ghetti, B. F., & Benson, M. D. (1991) · Science · doi:10.1126/science.1925564 · Cited by 1,142
Release of Excess Amyloid β Protein from a Mutant Amyloid β Protein Precursor
Cai, X.-D., Golde, T. E., & Younkin, S. G. (1993) · Science · doi:10.1126/science.8424174 · Cited by 913
Houslay, M. D., & Adams, D. R. (2003) · Biochemical Journal · doi:10.1042/bj20021698 · Cited by 768
Toward a molecular definition of long-term memory storage
Bailey, C. H., Bartsch, D., & Kandel, E. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13445 · Cited by 689
dunce, a mutant of Drosophila deficient in learning.
Dudai, Y., Jan, Y. N., Byers, D., Quinn, W. G., & Benzer, S. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.5.1684 · Cited by 619
Robakis, N. K. R. K., Ramakrishna, N., Wolfe, G. C., & Wisniewski, H. M. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.12.4190 · Cited by 603
Vitolo, O. V., Sant'Angelo, A., Costanzo, V., Battaglia, F., Arancio, O., & Shelanski, M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172504199 · Cited by 534
Byers, D., Davis, R. L., & Kiger, J. A. (1981) · Nature · doi:10.1038/289079a0 · Cited by 447
Structural Basis for the Activity of Drugs that Inhibit Phosphodiesterases
Card, G. L., England, B. P., Suzuki, Y., Fong, D., Powell, B., Lee, B., Luu, C. A., Tabrizizad, M., Gillette, S., Ibrahim, P. N., et al. (2004) · Structure · doi:10.1016/j.str.2004.10.004 · Cited by 444
Gong, B., Vitolo, O. V., Trinchese, F., Liu, S., Shelanski, M., & Arancio, O. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22831 · Cited by 442
Sette, C., & Conti, M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.28.16526 · Cited by 412
Burgin, A. B., Magnússon, Ó. Þ., Singh, J., Witte, P., Staker, B. L., Björnsson, J. M., Þorsteinsdóttir, M., Hrafnsdóttir, S., Hagen, T. J., Kiselyov, A. S., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1598 · Cited by 396
Self-citationJin, S.-L. C., & Conti, M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122041599 · Cited by 368
Regulation and organization of adenylyl cyclases and cAMP
COOPER, D. M. F. (2003) · Biochemical Journal · doi:10.1042/bj20031061 · Cited by 356
Targeting the CREB pathway for memory enhancers
Tully, T., Bourtchouladze, R., Scott, R., & Tallman, J. F. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1061 · Cited by 355
In vivo radioligand binding to translocator protein correlates with severity of Alzheimer’s disease
Kreisl, W. C., Lyoo, C. H., McGwier, M., Snow, J., Jenko, K. J., Kimura, N., Corona, W., Morse, C. L., Zoghbi, S. S., Pike, V. W., et al. (2013) · Brain · doi:10.1093/brain/awt145 · Cited by 350
cAMP-Specific Phosphodiesterase-4 Enzymes in the Cardiovascular System
Houslay, M. D., Baillie, G. S., & Maurice, D. H. (2007) · Circulation Research · doi:10.1161/01.res.0000261934.56938.38 · Cited by 318
Bolger, G. B., Michaeli, T., Martins, T., John, T. S., Steiner, B., Rodgers, L., Riggs, M. G., Wigler, M. H., & Ferguson, K. M. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.10.6558-6571.1993 · Cited by 317
Selective phosphodiesterase inhibitors: a promising target for cognition enhancement
Reneerkens, O. A. H., Rutten, K., Steinbusch, H. W. M., Blokland, A., & Prickaerts, J. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1273-x · Cited by 271
Specific Role of Phosphodiesterase 4B in Lipopolysaccharide-Induced Signaling in Mouse Macrophages
Jin, S.-L. C., Lan, L., Zoudilova, M., & Conti, M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.3.1523 · Cited by 256
Gervasi, N., Tchénio, P., & Préat, T. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.014 · Cited by 254
Chen, C. N., Denome, S. A., & Davis, R. L. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.24.9313 · Cited by 244
Li, Y., Cheng, Y., Huang, Y., Conti, M., Wilson, S. P., O’Donnell, J. M., & Zhang, H. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5236-10.2011 · Cited by 234
Pérez-Torres, S., Miró, X., Palacios, J. M., Cortés, R., Puigdomènech, P., & Mengod, G. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00097-1 · Cited by 231
Reversal of long-term dendritic spine alterations in Alzheimer disease models
Smith, D. L., Pozueta, J., Gong, B., Arancio, O., & Shelanski, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908706106 · Cited by 229
Morris, R., Pandya, D. Ν., & Petrides, M. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19990503)407:2 · Cited by 219
An anchored PKA and PDE4 complex regulates subplasmalemmal cAMP dynamics
Willoughby, D., Wong, W., Schaack, J. B., Scott, J. D., & Cooper, D. M. F. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601113 · Cited by 192
Terrin, A., Benedetto, G. D., Pertegato, V., Cheung, Y.-F., Baillie, G. S., Lynch, M. J., Elvassore, N., Prinz, A., Herberg, F. W., Houslay, M. D., et al. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200605050 · Cited by 192
Swinnen, J. V., JOSEPH, D. R., & Conti, M. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.14.5325 · Cited by 173
Hoffmann, R., Wilkinson, I., McCALLUM, J. F., ENGELS, P., & Houslay, M. D. (1998) · Biochemical Journal · doi:10.1042/bj3330139 · Cited by 165
Richter, W., Jin, S.-L. C., & Conti, M. (2005) · Biochemical Journal · doi:10.1042/bj20050030 · Cited by 161
Wang, C., Yang, X., Zhuo, Y., Zhou, H., Lin, H.-B., Cheng, Y., Xu, J., & Zhang, H. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711000836 · Cited by 153
Cloning and characterization of mammalian homologs of the Drosophila dunce+ gene.
Davis, R., Takayasu, H., Eberwine, M., & Myres, J. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.10.3604 · Cited by 146
GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses
Bruno, O., Fedele, E., Prickaerts, J., Parker, L. A., Canepa, E., Brullo, C., Cavallero, A., Gardella, E., Balbi, A., Domenicotti, C., et al. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01524.x · Cited by 137
Exome Sequencing Identifies PDE4D Mutations in Acrodysostosis
Lee, H., Graham, J. M., Rimoin, D. L., Lachman, R. S., Krejčı́, P., Tompson, S. W. J., Nelson, S. F., Krakow, D., & Cohn, D. H. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.03.004 · Cited by 136
Imanishi, T., Sawa, A., Ichimaru, Y., Miyashiro, M., Kato, S., Yamamoto, T., & Ueki, S. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(96)00969-7 · Cited by 130
Exome Sequencing Identifies PDE4D Mutations as Another Cause of Acrodysostosis
Michot, C., Goff, C. L., Goldenberg, A., Abhyankar, A., Klein, C., Kinning, E., Guerrot, A., Flahaut, P., Duncombe, A., Baujat, G., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.03.003 · Cited by 128
Beneficial effects of rolipram in the R6/2 mouse model of Huntington's disease
DeMarch, Z., Giampà, C., Patassini, S., Bernardi, G., & Fusco, F. R. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.02.010 · Cited by 121
Wang, H., Peng, M.-S., Chen, Y., Geng, J., Robinson, H. H., Houslay, M. D., Cai, J., & Ke, H. (2007) · Biochemical Journal · doi:10.1042/bj20070970 · Cited by 120
Linglart, A., Fryssira, H., Hiort, O., Holterhus, P., de Nanclares, G. P., Argente, J., Heinrichs, C., Kuechler, A., Mantovani, G., Leheup, B., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2326 · Cited by 116
Crystal structure of phosphodiesterase 4D and inhibitor complex1
Lee, M. E., Markowitz, J., Lee, J., & Lee, H. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)03396-3 · Cited by 114
Discovery of selective PDE4B inhibitors
Naganuma, K., Omura, A., Maekawara, N., Saitoh, M., Ohkawa, N., Kubota, T., Nagumo, H., Kodama, T., Takemura, M., Ohtsuka, Y., et al. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.04.121 · Cited by 111
Richter, W., & Conti, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203585200 · Cited by 110
Structural basis for the design of selective phosphodiesterase 4B inhibitors
Fox, D. N. A., Burgin, A. B., & Gurney, M. E. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.12.003 · Cited by 109
Self-citationCheng, Y., Wang, C., Lin, H.-B., Li, Y., Huang, Y., Xu, J., & Zhang, H. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1943-3 · Cited by 99
Ghosh, M., Garcia‐Castillo, D., Aguirre, V., Golshani, R., Atkins, C. M., Bramlett, H. M., Dietrich, W. D., & Pearse, D. D. (2012) · Glia · doi:10.1002/glia.22401 · Cited by 97
Monaco, L., Vicini, E., & Conti, M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42355-6 · Cited by 93
Mori, F., Pérez-Torres, S., De, R., Porzionato, A., Macchi, V., Beleta, J., Gavaldà, A., Palacios, J. M., & Mengod, G. (2010) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2010.03.004 · Cited by 91
Richter, W., & Conti, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312687200 · Cited by 90
Phosphodiesterase Inhibition Rescues Chronic Cognitive Deficits Induced by Traumatic Brain Injury
Titus, D. J., Sakurai, A., Kang, Y., Furones, C., Jergová, S., Santos, R., Sick, T. J., & Atkins, C. M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.5133-12.2013 · Cited by 80
Castro, L. R., Gervasi, N., Guiot, E., Cavellini, L., Nikolaev, V. O., Paupardin‐Tritsch, D., & Vincent, P. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5851-09.2010 · Cited by 78
cAMP microdomains and L‐type Ca2+ channel regulation in guinea‐pig ventricular myocytes
Warrier, S., Ramamurthy, G., Eckert, R. L., Nikolaev, V. O., Lohse, M. J., & Harvey, R. D. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2006.124891 · Cited by 65
Miró, X., Pérez-Torres, S., Puigdomènech, P., Palacios, J. M., & Mengod, G. (2002) · Synapse · doi:10.1002/syn.10100 · Cited by 57
Identification of Novel Mutations ConfirmsPde4das a Major Gene Causing Acrodysostosis
Lynch, D. C., Dyment, D. A., Huang, L., Nikkel, S. M., Lacombe, D., Campeau, P. M., Lee, B., Bacino, C. A., Michaud, J. L., Bernier, F. P., et al. (2012) · Human Mutation · doi:10.1002/humu.22222 · Cited by 56
Pangalos, M. N., Jacobsen, S. J., & Reinhart, P. H. (2005) · Biochemical Society Transactions · doi:10.1042/bst0330553 · Cited by 48
The cAMP-specific phosphodiesterase 4B mediates Aβ-induced microglial activation
Sebastiani, G., Morissette, C., Lagacé, C., Boulé, M., Ouellette, M., McLaughlin, R. W., Lacombe, D., Gervais, F., & Tremblay, P. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.024 · Cited by 45
Goto, T., Shiina, A., Yoshino, T., Mizukami, K., Hirahara, K., Suzuki, O., Sogawa, Y., Takahashi, T., Mikkaichi, T., Nakao, N., et al. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.03.104 · Cited by 40
Butler, M. G., Rames, L. J., & Wadlington, W. B. (1988) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320300416 · Cited by 33
Sutcliffe, J. S., Beaumont, V., Watson, J. M., Chew, C. S., Beconi, M. G., Hutcheson, D. M., Dominguez, C., & Muñoz-Sanjuán, I. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102449 · Cited by 31
Phosphodiesterase isoform‐specific expression induced by traumatic brain injury
Oliva, A. A., Kang, Y., Furones, C., Alonso, O. F., Bruno, O., Dietrich, W. D., & Atkins, C. M. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12049 · Cited by 29
Research works printed but not linked: 2
- Gong, 2004, Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment, J Clin Invest, 114, 1624, 10.1172/JCI22831 · DOI · Paper page
- Li, 2011, Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling, J Neurosci, 31, 172, 10.1523/JNEUROSCI.5236-10.2011 · DOI
Cited by
Sorted by citations
Tau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113
Huang, S., Ge, X., Yu, J., Han, Z., Yin, Z., Li, Y., Chen, F., Wang, H., Zhang, J., & Lei, P. (2018) · The FASEB Journal · doi:10.1096/fj.201700673r · Cited by 388
Role of tau protein in Alzheimer’s disease: The prime pathological player
Muralidar, S., Ambi, S. V., Sekaran, S., Thirumalai, D., & Palaniappan, B. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.07.327 · Cited by 278
Pharmacological Modulation of Functional Phenotypes of Microglia in Neurodegenerative Diseases
Song, G. J., & Suk, K. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00139 · Cited by 206
Prickaerts, J., Heckman, P. R. A., & Blokland, A. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1364360 · Cited by 172
Metadata
- Authors
- Gurney, M. E., D'Amato, E. C., & Burgin, A. B.
- Affiliations
- Tetra Therapeutics (United States) (US)
- Broad Institute (US)
- Corresponding author
- Gurney, Mark E.
- Venue
- Neurotherapeutics
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 12
- Issue
- 1
- Pages
- 49-56
- ISSN
- 1878-7479 (ISSN-L)
- PMC
- PMC4322084
- OpenAlex
- W2078329648
- Cited by
- 121
- References
- 75
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 14 · 2023: 11 · 2022: 6 · 2021: 6 · 2020: 12 · 2019: 11 · 2018: 12 · 2017: 16 · 2016: 8 · 2015: 6
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neurotherapeutics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R44MH091791, R43MH091791)
- National Institute of Neurological Disorders and Stroke (U01NS078034)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- phosphodiesterase 4, Alzheimer's disease, negative allosteric modulators, PDE4B, PDE4D, cAMP signaling, CREB, neuroinflammation, acrodysostosis, intellectual disability, memory consolidation
- MeSH terms
- Alzheimer Disease, Animals, Humans, Cyclic Nucleotide Phosphodiesterases, Type 4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
